Diphtheria remains a threat to health in the developing world: an overview

Mattos‐Guaraldi, Ana Luíza; Moreira, Lilian O.; Damasco, Paulo Vieira; Júnior, Raphael Hirata

doi:10.1590/s0074-02762003000800001

Cited by 86 publications

(94 citation statements)

References 35 publications

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“…Toxigenic strains are therefore associated with relatively high case fatality rates of between 5% and 10% in the general population. In children under 5 years, the elderly and immunocompromised individuals, the case fatality rate can reach approximately 20% [17,70,129].…”

Section: General Description Of Corynebacterium Diphtheriaementioning

confidence: 99%

The Evolution and Value of Diphtheria Vaccine

Bae¹

2011

KSBB Journal

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1) This review article provides an overview of the evolution of diphtheria vaccine, its value and its future. Diphtheria is an infectious illness caused by diphtheria toxin produced by pathogenic strains of Corynebacterium diphtheriae. It is characterized by a sore throat with membrane formation due to local tissue necrosis, which can lead to fatal airway obstruction; neural and cardiac damage are other common complications. Diphtheria vaccine was first brought to market in the 1920s, following the discovery that diphtheria toxin can be detoxified using formalin. However, conventional formalin-inactivated toxoid vaccines have some fundamental limitations. Innovative technologies and approaches with the potential to overcome these limitations are discussed in this paper. These include genetic inactivation of diphtheria toxoid, innovative vaccine delivery systems, new adjuvants (both TLRindependent and TLR-dependent adjuvants), and heat-and freeze-stable agents, as well as novel platforms for producing improved conventional vaccine, DNA vaccine, transcutaneous (microneedle-mediated) vaccine, oral vaccine and edible vaccine expressed in transgenic plants. These innovations target improvements in vaccine quality (efficacy, safety, stability and consistency), ease of use and/or thermal stability. Their successful development and use should help to increase global diphtheria vaccine coverage.

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Section: General Description Of Corynebacterium Diphtheriaementioning

confidence: 99%

The Evolution and Value of Diphtheria Vaccine

Bae¹

2011

KSBB Journal

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“…Indeed, loss of protective levels of antitoxin in the adult population was a major contributing factor in the diphtheria epidemic that occurred in the 1990's in states of the former Soviet Union (Golaz et al, 2000;Mattos-Guaraldi et al, 2003).…”

Section: Introductionmentioning

confidence: 99%

Bacteriophage-based vectors for site-specific insertion of DNA in the chromosome of Corynebacteria

Oram

Woolston

Jacobson

et al. 2007

Gene

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In Corynebacterium diphtheriae, diphtheria toxin is encoded by the tox gene of some temperate corynephages such as β. β-like corynephages are capable of inserting into the C. diphtheriae chromosome at two specific sites, attB1 and attB2. Transcription of the phage-encoded tox gene, and many chromosomally-encoded genes, is regulated by the DtxR protein in response to Fe 2+ levels. Characterizing DtxR-dependent gene regulation is pivotal in understanding diphtheria pathogenesis and mechanisms of iron-dependent gene expression; although this has been hampered by a lack of molecular genetic tools in C. diphtheriae and related Coryneform species. To expand the systems for genetic manipulation of C. diphtheriae, we constructed plasmid vectors capable of integrating into the chromosome. These plasmids contain the β-encoded attP site and the DIP0182 integrase gene of C. diphtheriae NCTC13129. When these vectors were delivered to the cytoplasm of nonlysogenic C. diphtheriae, they integrated into either the attB1 or attB2 sites with comparable frequency. Lysogens were also transformed with these vectors, by virtue of the second attB site. An integrated vector carrying an intact dtxR gene complemented the mutant phenotypes of a C. diphtheriae ΔdtxR strain. Additionally, strains of β-susceptible C. ulcerans, and C. glutamicum, a species non-permissive for β, were each transformed with these vectors. This work significantly extends the tools available for targeted transformation of both pathogenic and non-pathogenic Corynebacterium species.

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“…Keywords: diphtheria vaccines, C. diphtheriaе, diphtheria bacterial antigens, adhesion, electromagnetic radiation of microwave frequency Эпидемическое возвращение дифтерии в стра-нах Восточной Европы в 1990-х годах стало свидетельст-вом постоянной угрозы этого, как уже считалось к тому времени, редкого заболевания. Медицинское сообщест-во вынуждено было признать, что Corynebacterium diphtheriae все еще является глобальным медицинским вызо-вом, который требует пристального внимания и разра-ботки новых подходов для борьбы с инфекцией [1][2][3][4].…”

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“…Таким образом, искусственный активный антиток-сический иммунитет можно считать необходимым, но не достаточным условием защищенности от дифтерии. Под-тверждением этому может служить как важнейшая осо-бенность последней эпидемии дифтерии -возникнове-ние и развитие ее на фоне высоких показателей приви-тости и иммунности, так и существенная доля привитых лиц среди заболевших дифтерией в разных странах и в предшествующие годы [1,3,4]. Закономерно возникает вопрос о необходимости разработки новых средств им-мунопрофилактики дифтерии на основе изучения бакте-риальных антигенов, ответственных за формирование ре-зистентности организма к инвазии патогена [5,7].…”

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